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Overexpression of human insulin-like growth factor-I promotes new tissue formation in an ex vivo model of articular chondrocyte transplantation

Gene Therapy volume 8, pages 1443–1449 (2001)Cite this article

Abstract

Articular cartilage, the tissue that forms the gliding surface of joints, has a poor regenerative capacity. Insulin-like growth factor-I (IGF-I) is a polypeptide that is anabolic and mitogenic for cartilage. Transfection of articular chondrocytes with an expression plasmid vector containing the cDNA for human IGF-I under the control of the cytomegalovirus promoter/enhancer led to expression of the transgene and synthesis of biologically relevant amounts of IGF-I protein. Transplantation of transfected articular chondrocytes on to the surface of articular cartilage explants led to the formation of a new tissue layer on the cartilage explant surface. The new tissue was characterized by the presence of type II collagen and proteoglycan and by the absence of type I collagen, consistent with hyaline-like cartilage. The tissue formed by the chondrocytes expressing IGF-I was thicker and contained more cells than controls transfected with an expression plasmid vector containing the Escherichia coli (E. coli) β-galactosidase (lacZ) gene. Transplantation of articular chondrocytes that overexpress human IGF-I also increased DNA synthesis and the synthesis of glycosaminoglycans by the underlying explant cartilage chondrocytes. These results identify a mechanism by which IGF-I may simultaneously promote chondrogenesis and shift cartilage homeostasis in an anabolic direction. The data further suggest that therapeutic growth factor gene transfer may be applicable to articular cartilage. Gene Therapy (2001) 8, 1443–1449.

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Acknowledgements

Part of this work was presented at the 46th Annual Meeting of the Orthopaedic Research Society in Orlando, FL, 12–15 March 2000. We thank AJ D'Ercole and B Moats-Staats for the human IGF-I cDNA, C Trahan for help with histological processing and M Cucchiarini and L Weissbach for valuable discussions. The work was supported by the German Academy for Natural Scientists Leopoldina (BMBF-LPD 9801–10, HM) and NIH grants AR 31068 and AR 45749 (SBT).

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  1. H Madry

    Present address: Department of Orthopaedic Surgery, Laboratory of Experimental Orthopaedics, Saarland University Medical Center, Homburg, 6624, Germany

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Orthopaedic Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    H Madry & SB Trippel

  2. Departments of Biostatistics and Orthopaedic Surgery, Children's Hospital, Harvard Medical School, Boston, MA, USA

    D Zurakowski

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Madry, H., Zurakowski, D. & Trippel, S. Overexpression of human insulin-like growth factor-I promotes new tissue formation in an ex vivo model of articular chondrocyte transplantation. Gene Ther 8, 1443–1449 (2001). https://doi.org/10.1038/sj.gt.3301535

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